The Angiopoietin-Tie2 signaling pathway is a major regulator of vascular development, and altered expression of the Angiopoietin ligands or activity of the Tie2 receptor has been linked to a variety of vascular diseases and adverse outcomes in patients. In blood vascular endothelium, Angiopoietin2 is reported to function as a competitive antagonist of Angiopietin1/Tie2 signaling, inhibiting Angiopoietin1-mediated phosphorylation of Tie2.
Pharmaceuticals with agents which inhibit or modify kinases and therefore inhibit vascular development are used for treatment of some types of cancer as well as other diseases, such as neovascular glaucoma, abnormal ocular vasculatures and glaucoma generally as set out in U.S. Pat. Nos. 8,754,209, 8,529,943, 8,476,434, 8,450,305, 8,425,469, and 8,338,455; and U.S. patent application Ser. Nos. 14/119,532, 13/920,103, 14/131,024, and 13/652,154 (U.S. Patent Application Publication Nos. 2014/0161720, 2014/0004175, 2014/0163079, and 2013/0095105, respectively), each of which is hereby incorporated by reference in its entirety.
Knowledge of pathways regulating vascular development has been used to develop drugs for controlling this development. Knowledge of pathogenetic and molecular pathways leading to disease conditions can reveal methods of treating or preventing such conditions. For example, increased intraocular pressure (TOP) due to impaired aqueous humor drainage is a major risk factor for development of glaucoma, and determining the pathway by which this occurs would be helpful in finding other treatments. Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide.
Although inhibitory kinases haves been used to treat glaucoma, particularly neovascular glaucoma, there is a need to know the pathway that is active and leads to open angle glaucoma and congenital glaucoma in order to provide better treatment and prevention of this condition.